4-Methylmorpholine → 1-(3-ethyl-2-hydroxypentanoyl)-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)-L-prolinamide

HRID 1058285Notes

Reaction equation

HRID 1058285 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][C:11]=1[CH2:12][NH:13][C:14](=[O:20])[C@@H:15]1[CH2:19][CH2:18][CH2:17][NH:16]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:26][CH:27]([CH:31]([CH2:34][CH3:35])[CH2:32][CH3:33])[C:28](O)=[O:29].CN1CCOCC1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:32]([CH:31]([CH2:34][CH3:35])[CH:27]([OH:26])[C:28]([N:16]1[CH2:17][CH2:18][CH2:19][C@H:15]1[C:14]([NH:13][CH2:12][C:11]1[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:10]=1[CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])=[O:20])=[O:29])[CH3:33]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11428605L-prolin-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)amideHCID 225947313-ethyl-2-hydroxyPentanoic acid

Product 1

HCID 699399991-(3-ethyl-2-hydroxypentanoyl)-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)-L-prolinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of L-prolin-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)amide (171 mg, 0.47 mmol), 2-hydroxy-3-ethylpentanoic acid (68 mg, 0.47 mmol), and NMM (51 μL, 0.47 mmol) in DMF (5 mL) at ambient temperature under nitrogen atmosphere was added BOP reagent (247 mg, 0.56 mmol). The mixture was stirred at ambient temperature for 18 h. The solvent was removed under reduced pressure. The residue was partitioned between EtOAc and saturated aqueous NaHCO3. The EtOAc layer was separated, dried over anhydrous Na2SO4, and filtered. The filtrate solvent was removed under reduced pressure and the residue was purified by preparative thick layer silica gel plate chromatography (2000 μM×20 cm×20 cm) developed with 5% MeOH in dichloromethane. Desired bands were removed and eluted with 5% MeOH in dichloromethane. The filtrate solvent was concentrated in vacuo to obtain 1-(3-ethyl-2-hydroxypentanoyl)-N-(2-(tert-butyloxycarbonylaminomethyl)-5-chlorobenzyl)-L-prolinamide was obtained as a yellow oil (200 mg; HPLC RT=3.45 min, method A; LC-MS m/z=496.1).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customThe residue was partitioned between EtOAc and saturated aqueous NaHCO3
  3. customThe EtOAc layer was separated
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customThe filtrate solvent was removed under reduced pressure
  7. customthe residue was purified by preparative thick layer silica gel plate chromatography (2000 μM×20 cm×20 cm)
  8. customDesired bands were removed
  9. washeluted with 5% MeOH in dichloromethane
  10. concentrationThe filtrate solvent was concentrated in vacuo

Sources & evidence

ORD record
ord-e5e754a4a9424b7dbaf0b0073d059fc5
Source dataset
uspto-grants-2003_02
Patent number
US06515011B2

Reaction notes

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